Androgens synthesized in the testis and the adrenal cortex, bind to an androgen receptor at the target organ, and exert various physiological activities. Natural androgens all belong to C19 steroids chemically. The chief androgen among them is testosterone, which is synthesized at testis, incorporated into target cells and has strong physiological activity. For females, the adrenal cortex is a major source for androgens.
Androgens have actions of developing and maintaining the functions of reproductive organs (prostate, seminal vesicle, epididymis, vas deferens, etc.), sexual differentiation at fetal stage, formation of sperm, expression of secondary sexual characteristics (induction of masculinization for muscle/backbone, voice, fat distribution, etc.), promoting protein anabolism at muscle, etc., and actions for bone metabolism, etc. Therefore, insufficiency of androgen such as androgen deficiency by testis function disorders and castration, etc. is linked to various diseases and decrease of QOL (quality of life). For this, androgen supplement therapy is usually carried out. In addition to testosterone, synthetic androgens having different balance of androgen action have been investigated, and applied in clinical practice.
On the other hand, in the case that androgens are associated with the progress of diseases, androgen deprivation therapy is carried out. For example, for androgen-dependent prostate cancer, testosterone level is lowered by castration operation or GnRH agonist administration, to increase therapeutic effects.
In the case of androgen supplements, testosterone or synthetic androgens are usually used. However, these substances have steroid backbones, and sometimes give a great burden to the liver, or exhibit actions of other steroid hormones. Therefore, an androgen receptor modulator having non-steroidal backbone (especially, agonist) is considered to be useful for improving diseases by deficient androgen actions (hypogonadism, male climacteric disturbance, etc.) and in diseases which is expected to be improved by actions of androgen (osteoporosis, etc.).
Furthermore, the present inventors have investigated and found that if the testosterone level is lowered by a castration operation or GnRH agonist administration, there may be cancer acquiring growth ability under such a lowered testosterone, and in such cancer, androgen agonists exhibit anti-tumor actions conversely.
Therefore, the object of the present invention is to provide an androgen receptor modulator (especially, agonist) having a non-steroidal backbone, to solve such problems.